Treatment of disorders arising from genetic mutation

ABSTRACT

A method and composition for the treatment of disorders resulting from mutations in one or more genes. The composition includes L-Carnitine tartrate, pyridoxal-5′-phosphate, pyridoxine (Vitamin-B6), and fumaric acid.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of a U.S. Non-Provisional patent application Ser. No. 17/367,606 filed on Jul. 5, 2021, which is incorporated herein by reference in its entirety

FIELD OF INVENTION

The present invention relates to a method of treatment, and more particularly, the present invention relates to the treatment of disorders arising from specific gene mutations.

BACKGROUND

The field of epigenetics is now key in the research and development of therapies to address pathology in the cells of living organisms. Understanding of various epigenetic mechanisms, like histone modification, DNA methylation, small non-coding RNAs, and gene functionality and regulation has revealed the pathophysiology of various disorders. Research has documented those mutations affecting the DNA Damage Recovery Pathways often lead to mutations in genes as well as alterations in epigenetic signaling of genes including BRCA1, BRCA2. Together, these mutations and signaling abnormalities turn off apoptosis signals or turn on senescence signals that leave these cells susceptible to mutation, infection, and toxins. Current genetic scanning technology detects these cellular conditions as abnormal gene sequences, single nucleotide polymorphisms, abnormal morphologies, abnormal protein folding patterns and decreased functionality. In some cases, these mutations are somatic cell abnormalities only, and their resolution resolves the present disease condition. However, some mutations are germline mutations that, if not corrected, will possibly be inherited by future generations.

In the case of viral infections, many attempts have been made at producing vaccines, with limited success. In the case of Human Papillomavirus (HPV), Herpes Simplex Virus (HSV), Simian Virus (SV), Human Immunodeficiency Virus (HIV), Coronavirus and viral Hepatitis, few agents are effective at halting the progression of an active infection and none are known to succeed at destroying the virus in the cell.

In the case of bacterial infections, the growing phenomenon of drug-resistant microbes is presenting new challenges to those battling bacterial infections. For example, the growing proportion of patients with drug-resistant, hospital-acquired infections and the growing number of people exhibiting Tuberculosis (TB) infections that are either multiple drug-resistant (MDR) or extensively drug-resistant (XDR) present a challenge of near-crisis proportions.

Hence, there is a need for a therapeutic agent that can be easily administered and is effective in the treatment of viral and bacterial infections and in possibly preventing and treating genetic disorders.

A list of the genes that are subject to regulation includes APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, DICER1, EPCAM, FH, GREM1, HOXB13, MITF, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, POLD1, POLE, PPM1D, PTCH1, PTEN, RAD51C, RAD51D, SMAD4, STK11 and TP53. Table 1 describes the function of the above genes and the health condition(s) that can result from mutations and/or other dysregulations.

TABLE 1 Genes and their functions Gene Gene function and conditions arising from mutations. APC The APC Gene provides instructions for making the APC protein, which plays a WNT signaling critical role in several cellular processes. The APC protein acts as a tumor pathway suppressor, which means that it keeps cells from growing and dividing too fast regulator or in an uncontrolled way. It helps control how often a cell divides, how it attaches to other cells within a tissue and whether a cell moves within or away from a tissue. This protein also helps ensure that the number of chromosomes in a cell is correct following cell division. The APC protein accomplishes these tasks mainly through association with other proteins, especially those that are involved in cell attachment and signaling. One protein with which APC associates is beta-catenin. Beta-catenin helps control the activity (expression) of particular genes and promotes the growth and division (proliferation) of cells and the process by which cells mature to carry out specific functions (differentiation). Beta-catenin also helps cells attach to one another and is important for tissue formation. Association of APC with beta-catenin signals for beta-catenin to be broken down when it is no longer needed. Mutations associated with cancers: Turcot Syndrome, gastric cancers, primary macronodular adrenal hyperplasia. Mutations associated with other conditions: desmoid tumors associated familial adenomatous polyposis (FAP). Most people with FAP will develop colorectal cancer. ATM: The ATM Gene provides instructions for making a protein that is located serine/threonine primarily in the nucleus of cells where it helps control the rate at which cells kinase grow and divide. This protein also plays an important role in the normal development and activity of several body systems, including the nervous system and the immune system. Additionally, the ATM protein assists cells in recognizing damaged or broken DNA strands. DNA can be damaged by agents such as toxic chemicals or radiation. Breaks in DNA strands also occur naturally when chromosomes exchange genetic material during cell division. The ATM protein coordinates DNA repair by activating enzymes that fix the broken strands. Efficient repair of damaged DNA strands helps maintain the stability of the cell's genetic information. Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research. ATM mutations can allow cells to die inappropriately, particularly affecting cells in a part of the brain involved in coordinating movements (the cerebellum). This loss of brain cells causes the movement problems characteristic of ataxia-telangiectasia. Mutations associated with cancers: bladder, breast, melanoma, stomach, pancreas, lung, ovaries. BAP1 Although the exact mechanism is unclear, the BAP1 protein acts as a tumor BRCA1 suppressor. Tumor suppressor proteins help prevent cells from growing and associated dividing too rapidly or in an uncontrolled way. Although it is unclear exactly protein 1 how changes in BAP1 function lead to BAP1 tumor predisposition syndrome, researchers speculate that altered activity of proteins normally regulated by BAP1 deubiquitination may promote cell proliferation or survival, resulting in tumor formation. Mutations associated with cancers: cholangiocarcinoma, melanoma, uveal melanoma. BARD1 The BRCA1-BARD1 heterodimer specifically mediates the formation of ‘Lys-6’- BRCA1 linked polyubiquitin chains and coordinates a diverse range of cellular associated RING pathways such as DNA damage repair, ubiquitination and transcriptional domain 1 regulation to maintain genomic stability. Plays a central role in the control of the cell cycle in response to DNA damage. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing and RNAP II stability by inhibiting pre-mRNA 3′ cleavage. Mutations associated with cancers: neuroblastoma, ovarian, breast. BMPR1A: The bone morphogenetic protein receptor type 1A has a specific site into bone which certain other proteins called ligands, fit like keys into locks. Specifically, morphogenetic the BMPR1A protein attaches (binds) to ligands in the transforming growth protein receptor factor beta (TGF-β) pathway. This signaling pathway allows the environment type 1A outside the cell to affect how the cell produces other proteins. The BMPR1A receptor protein and its ligands are involved in transmitting chemical signals from the cell membrane to the nucleus. Mutations associated with other conditions: Juvenile Polyposis Syndrome BRCA1: The BRCA1 Gene provides instructions for making a protein that acts as a Breast Cancer 1 tumor suppressor. Tumor suppressor proteins help prevent cells from growing DNA repair and dividing too rapidly or in an uncontrolled way. associated The BRCA1 protein is involved in repairing damaged DNA. In the nucleus of many types of normal cells, the BRCA1 protein interacts with several other proteins to mend breaks in DNA. Mutations associated with cancers: breast, ovarian, prostate, pancreatic, colon. BRCA2: The BRCA2 Gene provides instructions for making a protein that acts as a Breast Cancer 2 tumor suppressor. Tumor suppressor proteins help prevent cells from growing DNA repair and dividing too rapidly or in an uncontrolled way. associated The BRCA2 protein is involved in repairing damaged DNA. In the nucleus of many types of normal cells, the BRCA2 protein interacts with several other proteins to mend breaks in DNA. Mutations associated with cancers: breast, ovarian, prostate, pancreatic, melanoma. Mutations associated with other conditions: Fanconi anemia BRIP1: DNA-dependent ATPase and 5′ to 3′ DNA helicase required for the BRCA1 maintenance of chromosomal stability. Acts late in the Fanconi anemia interacting pathway, after FANCD2 ubiquitination. Involved in the repair of DNA double- protein C- strand breaks by homologous recombination in a manner that depends on its terminal association with BRCA1. helicase 1 Mutations associated with cancers: ovarian, breast. Mutations associated with other conditions: Fanconi anemia CDH1: The CDH1 Gene provides instructions for making a protein called epithelial cadherin 1 cadherin or E-cadherin. This protein is found within the membrane that surrounds epithelial cells, which are the cells that line the surfaces and cavities of the body, such as the inside of the eyelids and mouth. E-cadherin belongs to a family of proteins called cadherins whose function is to help neighboring cells stick to one another (cell adhesion) to form organized tissues. Mutations associated with cancers: breast, hereditary gastric diffuse cancer, ovarian, prostate, endometrial. Mutations associated with other conditions: Blepharocheilodontic (BCD) Syndrome, cleft lip and palate. CDK4: Mutations in this gene as well as in its related proteins including D-type cyclin cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis dependent of a variety of cancers. kinase 4 Mutations associated with cancers: melanoma, cutaneous malignant melanoma. CDKN2A: The CDKN2A gene provides instructions for making several proteins. The most cyclin well-studied are the p16(INK4A) and the p14(ARF) proteins. Both function as dependent tumor suppressors, which means they keep cells from growing and dividing kinase inhibitor too rapidly or in an uncontrolled way. Both proteins are also involved in 2A stopping cell division in older cells (senescence). Mutations associated with cancers: bladder, head and neck squamous cell, lung, melanoma. CHEK2: The protein encoded by this gene is a cell cycle checkpoint regulator and checkpoint putative tumor suppressor. It contains a forkhead-associated protein kinase 2 interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations associated with cancers: Li-fraumeni Syndrome, ovarian, prostate, breast. DICER1: The DICER1 gene provides instructions for making a protein that plays a role in ribonuclease III regulating the activity (expression) of other genes. The Dicer protein aids in the production of a molecule called microRNA (miRNA). MicroRNAs are short lengths of RNA, a chemical cousin of DNA. Dicer cuts (cleaves) precursor RNA molecules to produce miRNA. Mutations associated with cancers: lungs, kidneys, ovaries, thyroid. EPCAM: The EPCAM Gene provides instructions for making a protein known as epithelial cell epithelial cellular adhesion molecule (EpCAM). This protein is associated with adhesion epithelial cells, which are the cells that line the surfaces and cavities of the molecule body. The EpCAM protein is found spanning the membrane that surrounds epithelial cells, where it helps cells stick to one another (cell adhesion). In addition, the protein in the cell membrane can be cut at a specific location, releasing a piece called the intracellular domain (EplCD), which helps relay signals from outside the cell to the nucleus of the cell. EplCD travels to the nucleus and joins with other proteins, forming a group (complex) that regulates the activity of several genes that are involved in many cell processes, including growth and division (proliferation), maturation (differentiation), and movement (migration), all of which are important processes for the proper development of cells and tissues. Mutations associated with other conditions: Lynch Syndrome, congenital tufting enteropathy. FH: The FH Gene provides instructions for making an enzyme called fumarase (also fumarate known as fumarate hydratase). Fumarase participates in an important series of hydratase reactions known as the citric acid cycle or Krebs cycle, which allows cells to use oxygen and generate energy. Specifically, fumarase helps convert a molecule called fumarate to a molecule called malate. Mutations associated with cancers: Hereditary leiomyomatosis and renal cell cancer, primary macronodular adrenal hyperplasia. Mutations associated with other conditions: Fumarase deficiency GREM1: As an antagonist of BMP (bone morphogenic protein), this gene may play a gremlin 1, DAN role in regulating organogenesis, body patterning, and tissue differentiation. In family BMP mouse, this protein has been shown to relay the sonic hedgehog (SHH) signal antagonist from the polarizing region to the apical ectodermal ridge during limb bud outgrowth. Mutations associated with other conditions: Polyposis Syndrome HOXB13: The HOXB13 Gene provides instructions for producing a protein that attaches Homeobox B13 (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this role, the protein produced from the HOXB13 Gene is called a transcription factor. The HOXB13 protein is part of a large group of transcription factors called the homeobox protein family. The HOXB13 protein is thought to play a role in the development and maintenance of the skin. It also acts as a tumor suppressor, which means that it keeps cells from growing and dividing too fast or in an uncontrolled way. Mutations associated with cancer: prostate MITF: The MITF Gene provides instructions for making a protein called melanocyte melanocyte inducing transcription factor. This protein plays a role in the development, inducing survival and function of certain types of cells. To carry out this role, the protein transcription attaches to specific areas of DNA and helps control the activity of particular factor genes. On the basis of this action, the protein is called a transcription factor. Mutations associated with cancer: melanoma Mutations associated with other conditions: Tietzee Syndrome, Waardenburg Syndrome MLH1: The MLH1 Gene provides instructions for making a protein that plays an mutL homolog 1 essential role in repairing DNA. This protein helps fix errors that are made when DNA is copied (DNA replication) in preparation for cell division. It is a mismatch repair gene. Mutations associated with cancer: ovarian syndrome, Lynch Syndrome, constitutional mismatch repair deficiency syndrome MSH2: The MSH2 Gene provides instructions for making a protein that plays an mutS homolog 2 essential role in repairing DNA. This protein helps fix errors that are made when DNA is copied (DNA replication) in preparation for cell division. Mutations associated with cancer: Ovarian Syndrome, Lynch Syndrome, constitutional mismatch repair deficiency syndrome MSH6: The MSH6 Gene provides instructions for making a protein that plays an mutS homolog 6 essential role in repairing DNA. This protein helps fix errors that are made when DNA is copied (DNA replication) in preparation for cell division. Mutations associated with cancer: Ovarian Syndrome, Lynch Syndrome, constitutional mismatch repair deficiency syndrome. MUTYH: The MUTYH Gene provides instructions for making an enzyme called MYH mutY DNA glycosylase, which is involved in the repair of DNA. This enzyme corrects glycosylase particular errors that are made when DNA is copied (DNA replication) in preparation for cell division Mutations associated with other conditions: familial adenomatous polyposis NBN: The MRE11A/RAD50/NBN complex interacts with the protein produced from nibrin the ATM Gene, which plays an essential role in recognizing broken strands of DNA and coordinating their repair. Mutations associated with cancer: breast, prostate, ovarian, melanoma, leukemia. NF1: The NF1 Gene provides instructions for making a protein called neurofibromin. Neurofibromin 1 This protein is produced in many types of cells, including nerve cells and specialized cells called oligodendrocytes and Schwann cells that surround nerves. These specialized cells form myelin sheaths, which are the fatty coverings that insulate and protect certain nerve cells. Mutations associated with cancer: Lung, Juvenile Myelomonocytic Leukemia Mutations associated with other conditions: Neurofibromatosis Type 1 PALB2: This gene encodes a protein that may function in tumor suppression. This Partner and protein binds to and colocalizes with the breast cancer 2 early onset protein localizer of (BRCA2) in nuclear foci and likely permits the stable intranuclear localization BRCA2 and accumulation and repair of BRCA2. Mutations associated with cancer: ovarian, breast, pancreatic. Mutations associated with other conditions: Fanconi anemia PMS2: The PMS2 Gene provides instructions for making a protein that plays an PMS1 homolog essential role in repairing DNA. This protein helps fix errors that are made 2, mismatch when DNA is copied (DNA replication) in preparation for cell division. The repair system PMS2 protein joins with another protein called MLH1 (produced from component the MLH1 Gene) to form a two-protein complex called a dimer. This complex coordinates the activities of other proteins that repair errors made during DNA replication. Repairs are made by removing the section of DNA that contains errors and replacing it with a corrected DNA sequence. The PMS2 gene is a member of a set of genes known as the mismatch repair (MMR) genes. Mutations associated with cancer: Ovarian Cancer, constitutional mismatch repair deficiency syndrome, Lynch Syndrome Mutations associated with other conditions: alopecia areata POLD1: DNA polymerase delta 1, catalytic subunit DNA polymerase This gene encodes the 125-kDa catalytic subunit of DNA polymerase delta. delta 1, catalytic DNA polymerase delta possesses both polymerase and 3′ to 5′ exonuclease subunit activity and plays a critical role in DNA replication and repair. Mutations associated with cancers: mandibular hypoplasia, Lipodystrophy Syndrome, Colorectal Cancer 10 Mutations associated with other conditions: deafness, progeroid features. POLE: This gene encodes the catalytic subunit of DNA polymerase epsilon. The DNA polymerase enzyme is involved in DNA repair and chromosomal DNA replication. epsilon, catalytic Mutations associated with cancer: Colorectal Cancer 12. subunit Mutations associated with other conditions: facial dysmorphism, immunodeficiency, livedo, short stature, intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies. PPM1D: The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein protein phosphatases. PP2C family members are known to be negative phosphatase, regulators of cell stress response pathways. The expression of this gene is Mg2+/Mn2+ induced in a p53-dependent manner in response to various environmental dependent 1D stresses. While being induced by tumor suppressor protein TP53/p53, this phosphatase negatively regulates the activity of p38 MAP kinase, MAPK/p38, through which it reduces the phosphorylation of p53 and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis. Mutations associated with cancer: Familial breast Mutations associated with other conditions: Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold PTCH1: Patched-1 and Sonic Hedgehog function in a pathway that is essential for early Patched 1 development. This pathway plays a role in cell growth, cell specialization, and determining the shape (patterning) of many different parts of the developing body. When Sonic Hedgehog is not present, patched-1 prevents cells from growing and dividing (proliferating). When Sonic Hedgehog is attached, patched-1 stops suppressing cell proliferation. Based on its role in preventing cells from proliferating in an uncontrolled way, PTCH1 is called a tumor suppressor gene. Mutations associated with cancer: basal cell carcinoma, skin, medulloblastoma, breast, colon, 9q22.3 microdeletion Mutations associated with other conditions: coloboma, nonsyndromic holoprosencephaly, Gorlin Syndrome. PTEN: The PTEN Gene provides instructions for making an enzyme that is associated phosphatase with almost all tissues in the body. The enzyme acts as a tumor suppressor, and tensin which means that it helps regulate cell division by keeping cells from growing homolog and dividing too rapidly or in an uncontrolled way. The PTEN enzyme modifies other proteins and fats (lipids) by removing phosphate groups, each of which consists of three oxygen atoms and one phosphorus atom. Enzymes with this function are called phosphatases. Mutations associated with cancer: prostate, endometrial, glioblastomas, astrocytomas, melanoma, bladder, lung, breast, head and neck squamous cell. Mutations associated with other conditions: autism spectrum disorder, Cowden Syndrome, Bannayan-Riley-Ruvalcaba Syndrome. RAD51C Essential for the homologous recombination (HR) pathway of DNA repair. RAD51 paralog C Involved in the homologous recombination repair (HRR) pathway of double- stranded DNA breaks arising during DNA replication or induced by DNA- damaging agents. Part of the RAD21 paralog protein complexes BCDX2 and CX3 which act at different stages of the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 seems to act downstream of BRCA2 recruitment and upstream of RAD51 recruitment; CX3 seems to act downstream of RAD51 recruitment; both complexes bind predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junction of replication forks. Mutations associated with cancer: Fanconi anemia, ovarian cancer, breast cancer. RAD51D: Involved in the homologous recombination repair (HRR) pathway of double- RAD51 paralog D stranded DNA breaks arising during DNA replication or induced by DNA- damaging agents. Bind to single-stranded DNA (ssDNA) and has DNA- dependent ATPase activity. Part of the Rad21 paralog protein complex BCDX2 which acts in the BRCAl-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment. Mutations associated with cancer: ovarian, breast-ovarian - familial 4. SMAD4: The SMAD4 protein serves both as a transcription factor and as a tumor SMAD family suppressor. Transcription factors help control the activity of particular genes, member 4 and tumor suppressors keep cells from growing and dividing too fast or in an uncontrolled way. Mutations associated with cancer: cholangiocarcinoma Mutations associated with other conditions: juvenile polyposis and blood vessel abnormalities other than hereditary hemorrhagic telangiectasia, hereditary hemorrhagic telangiectasia, Myhre Syndrome. STK11: The STK11 Gene (also called LKB1) provides instructions for making an enzyme serine/threonine called serine/threonine kinase 11. This enzyme is a tumor suppressor, which kinase 11 means that it helps keep cells from growing and dividing too fast or in an uncontrolled way. This enzyme helps certain types of cells correctly orient themselves within tissues (polarization) and assists in determining the amount of energy a cell uses. This kinase also promotes a type of programmed cell death known as apoptosis. In addition to its role as a tumor suppressor, serine/threonine kinase 11 function appears to be required for normal development before birth. Mutations associated with cancer: Lung, breast, ovarian, non-small cell lung carcinoma, cervix, colorectal, melanoma, pancreatic. Mutations associated with other conditions: Peutz-Jeghers Syndrome TP53: The TP53 Gene provides instructions for making a protein called tumor protein Tumor protein p53 (or TP53). This protein acts as a tumor suppressor, which means that it p53 regulates cell division by keeping cells from growing and dividing (proliferating) too fast or in an uncontrolled way. The p53 protein is located in the nucleus of cells throughout the body where it attaches (binds) directly to DNA. When the DNA in a cell becomes damaged by agents such as toxic chemicals, radiation or ultraviolet (UV) rays from sunlight, this protein plays a critical role in determining whether the DNA will be repaired or the damaged cell will self-destruct (undergo apoptosis). If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis. By stopping cells with mutated or damaged DNA from dividing, p53 helps prevent the development of tumors. Mutations associated with cancer: brain tumor, colorectal, liver, osteosarcoma, rhabdomyosarcoma, adrenocortical carcinoma, melanoma, lung, bladder, breast, kidney (Wilms' Tumor), Li-Fraumeni Syndrome, cholangiocarcinoma, head and neck squamous cell carcinoma.

Example list of viruses includes Human Papillomavirus (HPV), Herpes Simplex Virus (HSV), Simian Virus (SV), Coronavirus including SARS-Coronavirus, MERS-Coronavirus and SARS-COV2 (COVID-19) Coronavirus, Human Immunodeficiency Virus (HIV), Hepatitis Types A, B and C (Hep A, Hep B, Hep C). Example list of bacteria includes Mycoplasma and Tuberculosis (TB) (including MDR TB and XDR TB).

SUMMARY OF THE INVENTION

The following presents a simplified summary of one or more embodiments of the present invention in order to provide a basic understanding of such embodiments. This summary is not an extensive overview of all contemplated embodiments and is neither intended to identify key nor critical elements of all embodiments nor delineate the scope of any or all embodiments. Its sole purpose is to present some concepts of one or more embodiments in a simplified form as a prelude to the more detailed description that is presented later.

The principal object of the present invention is therefore directed to a method for addressing disorders arising from genetic mutations.

It is another object of the present invention that the composition can be easily administered.

It is still another object of the present invention that the method can be used to treat bacterial infections.

It is yet another object of the present invention that the method can be used to treat viral infections.

In one aspect, disclosed is a method of treating diseases and disorders resulting from genetic mutation, bacteria, and viruses. The method includes a step of administering a composition. The composition includes a dry admixture of L-Carnitine tartrate [CAS 36687-82-8], pyridoxal-5′-phosphate [CAS 54-47-7], fumaric acid [CAS 110-17-8], and Pyridoxine (Vitamin-B6). The composition is also referred to herein as D-Boramine+.

In one aspect, the composition can be used to treat the disorders resulting from dysregulation/mutation of APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, DICER1, EPCAM, FH, GREM1, HOXB13, MITF, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, POLD1, POLE, PPM1D, PTCH1, PTEN, RAD51C, RAD51D, SMAD4, STK11 and TP53 genes.

In one aspect, the composition can be used in the treatment of diseases resulting from infestation by Human Papillomavirus (HPV), Herpes Simplex Virus (HSV), Simian Virus (SV), Coronavirus including SARS-Coronavirus, MERS-Coronavirus and SARS-COV2 (COVID-19) Coronavirus, Human Immunodeficiency Virus (HIV), Hepatitis Types A, B and C (Hep A, Hep B, Hep C), Mycoplasma and Tuberculosis (TB) (including MDR TB and XDR TB).

In one aspect, the disclosed composition can be used in the treatment of cancers, Antiphospholipid Syndrome, disseminate intravascular coagulation (DIC), familial adenomatous polyposis, familial adenomatous polyposis, neurofibromatosis Type 1, alopecia areata, deafness, coloboma, Nonsyndromic holoprosencephaly, Gorlin Syndrome, autism spectrum disorder, Cowden Syndrome, Bannayan-Riley-Ruvalcaba Syndrome, hereditary hemorrhagic telangiectasia, Myhre Syndrome, Juvenile and Adult Polyposis Syndrome, Tietzee Syndrome, Waardenburg Syndrome, Fancomi anemia, Blepharocheilodontic (BCD) Syndrome, Lynch Syndrome, congenital tufting enteropathy, and fumarase deficiency.

In one aspect, the composition can be administered orally. However, other routes of administration are within the scope of the present invention.

These and other objects and advantages of the embodiments herein and the summary will become readily apparent from the following detailed description.

DETAILED DESCRIPTION

Subject matter will now be described more fully hereinafter. Subject matter may, however, be embodied in a variety of different forms and, therefore, covered or claimed subject matter is intended to be construed as not being limited to any exemplary embodiments set forth herein; exemplary embodiments are provided merely to be illustrative. Likewise, a reasonably broad scope for claimed or covered subject matter is intended. Among other things, for example, the subject matter may be embodied as methods, devices, components or systems. The following detailed description is, therefore, not intended to be taken in a limiting sense.

The word “exemplary” is used herein to mean “serving as an example, instance or illustration.” Any embodiment described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments. Likewise, the term “embodiments of the present invention” does not require that all embodiments of the invention include the discussed feature, advantage, or mode of operation.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of embodiments of the invention. As used herein, the singular forms “a,” “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises,” “comprising,” “includes” and/or “including” when used herein, specify the presence of stated features, integers, steps, operations, elements and/or components but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components and/or groups thereof.

The following detailed description includes the best currently-contemplated mode or modes of carrying out exemplary embodiments of the invention. The description is not to be taken in a limiting sense but is made merely for the purpose of illustrating the general principles of the invention, since the scope of the invention will be best defined by the allowed claims of any resulting patent.

Disclosed is a method for the treatment of disorders arising from genetic mutations. The composition includes a dry admixture of L-Carnitine tartrate, pyridoxal-5′-phosphate, pyridoxine (Vitamin B6) and fumaric acid. The disclosed composition may include L-Carnitine tartrate in a range of about 34-90%, pyridoxal-5′-phosphate in a range of about 5-33%, fumaric acid in a range of about 0.5-33%, and pyridoxine in a range of about 5-33%. The disclosed composition may act by entering somatic and germline cells and enabling the mitochondria to repair the defects and restore non-mutated homeostasis to the cell and its intracellular signaling.

The disclosed composition demonstrated success in improving gene functionality and resolving genetic deficiency in above listed SNPs, thus making way to correct the mutations over time Experiments were performed to evaluate the effectiveness of the composition in encoding for proteins and correcting genetic SNPs that drive essential biological processes, such as development and differentiation, and when dysregulated, the potential development of complex diseases. Overall, 36,900 tests were performed by PCR to determine gene functionality in the genes listed in Table 2. All genes that were tested having functionality less than 80 percent were included in the study. Within 12 months, all genes tested previously had improved to at least a 93-100 percent functionality. This method can help elucidate previously undetected changes occurring in disease states, in response to therapeutics, under different environmental conditions. Overall, 36,900 tests were performed on the genes listed in Table 2 to confirm greater than 92.99% functionality after taking an average dose of 1,000 mg per day of the disclosed composition for up to one year. Outcomes studies revealed gene function to improve in all SNPs tested thus suggesting a strong possibility of decreasing the chance of disease expression or decreasing severity of the active disease. All the genes listed in Table 2 (below) confirmed adequate functionality within 12 months to possibly aid in disease prevention or recovery. Table 2 shows the list of genes evaluated and the functionality of the genes before administering the disclosed composition; and after supplementing with the disclosed composition for up to one year, improvement in functionality increased to as much as 93 to 100 percent.

TABLE 2 Genes identified in the study, the number of mutations of each gene, the average functionality in the initial gene testing and the post-supplementation average functionality after 12 months of supplementation with the disclosed composition: Gene Mutations Avg initial f(x)* 12 months later f(x)* APC 111 <80% 93-100% ATM 63 <80% 93-100% BAP1 48 <80% 93-100% BARD1 57 <80% 93-100% BMPR1A 47 <80% 93-100% BRCA1 56 <80% 93-100% BRCA2 53 <80% 93-100% BRIP1 33 <80% 93-100% CDH1 57 <80% 93-100% CDK4 34 <80% 93-100% CDKN2A 35 <80% 93-100% CHECK2 34 <80% 93-100% DICER1 11 <80% 93-100% EPCAM 66 <80% 93-100% FH 40 <80% 93-100% GREM1 19 <80% 93-100% HOXB13 8 <80% 93-100% MITF 20 <80% 93-100% MLH1 50 <80% 93-100% MSH2 51 <80% 93-100% MSH6 40 <80% 93-100% MUTYH 11 <80% 93-100% NBN 19 <80% 93-100% NF1 12 <80% 93-100% PALB2 19 <80% 93-100% PMS2 26 <80% 93-100% POLD1 12 <80% 93-100% POLE 5 <80% 93-100% PPM1D 19 <80% 93-100% PTCH1 4 <80% 93-100% PTEN 47 <80% 93-100% RAD51C 25 <80% 93-100% RAD51D 9 <80% 93-100% SMAD4 33 <80% 93-100% STK11 44 <80% 93-100% TP53 52 <80% 93-100% *F(x) refers to functionality, All of the genes were tested an average of 2.5 times

The above experiment suggests that DNA on the SNPs tested with revealed decreased functionality were low in L-Carnitine tartrate, fumaric acid, pyridoxal-5′-phosphate, and pyridoxine. The disclosed composition was successful in improving functionality in the above listed SNPs and may correct the mutations over time. L-Carnitine tartrate with pyridoxal-5′-phosphate, fumaric acid, and pyridoxine improved gene functionality up to 100 percent with no overexpression noted.

L-Carnitine increases the proliferative responses of both murine and human lymphocyte following mitogenic stimulation and increase polymorphonuclear chemotaxis. L-Carnitine assists with fatty acid transport across the cell membrane and improves mitochondrial function. Furthermore, L-Carnitine, even at minimal concentrations, neutralizes the lipid induced immunosuppression.

Pyridoxine (Vitamin B6) in the disclosed composition can prevent impairment of nucleic acid synthesis and depresses antibody formation, delayed hypersensitivity reactions and the ability of phagocytes to kill bacteria. Thus, the pyridoxine may upregulate the immune system enhancing carnitine function.

Fumaric acid is an acid regulatory thus likely creating a healthier pH in the cell. Much like Vitamin D, fumaric acid is formed by the body, in the skin during exposure to sunlight. It is related to malic acid and is involved in the production of energy derived from food. Fumaric acid is an intermediate product of the citric acid cycle that is a source of intracellular energy in the form of adenosine triphosphate (ATP). It is generated by oxidation of adenylsuccinate by the enzyme succinate dehydrogenase and is then converted to maleate by the enzyme fumarase. At present, fumaric acid esters (FAE) are licensed for the treatment of psoriasis. Several lines of evidence have demonstrated immunomodulatory effects for FAE. Clinical studies in psoriasis showed a reduction of peripheral CD4+- and CD8+-T-lymphocytes due to the ability of FAE to induce apoptosis. In vitro studies with the ester dimethyl fumarate (DMF) described an inhibitory effect on nuclear factor kappa B (NF-κB)-dependent transcription of tumor necrosis factor-alpha (TNF-α) induced genes in human endothelial cells. Animal studies using a model of central nervous system demyelination, MOG-induced experimental autoimmune encephalomyelitis (EAE), revealed a reduction of microglia and macrophages in inflamed lesions. A clinical study in relapsing-remitting multiple sclerosis (RRMS) patients with a modified fumaric acid ester, BG-12, showed as “proof of principle” a significant reduction in the number of gadolinium enhancing lesions after 24 weeks of treatment as compared to placebo.

The disclosed method includes a step of administering the composition through one of the different routes of administration known in the art for administering medicine in humans. Preferably, the composition can be administered through an oral route. The composition can be formulated in oral or liquid forms for oral administration to humans. Examples of the liquid formulation can include suspensions, syrups and like. Examples of solid dosage forms can include tablets and capsules. The formulation may also include other ingredients which are substantially neutral and used for formulating the desired dosage form. Such ingredients are generally referred to as excipients. The disclosed dosage forms can be prepared by any of the methods known in the art of formulating oral dosage forms without departing from the scope of the present invention. The dose of disclosed composition in humans can be determined by known methods in the art. It is known that the actual dose may depend on the age and weight of a patient. In one case, the nominal adult dose of the disclosed composition may be in a range of about 500-1,000 mg/day. Depending on the specific condition and clinical presentation, a patient's daily dosage regimen may be adjusted from this nominal dose. Coronavirus, for example, responds well to a dose of 3,000 mg/day for predetermined number of days. The response to the treatment in a patient can optionally be evaluated using a suitable PCR test, the functioning of such PCR test is known to a skilled person.

Clinically, the disclosed composition has shown to be useful as a therapeutic agent in treating a variety of viral diseases, cancers and other diseases and in the permanent correction of certain regulatory genetic mutations to somatic and germline cells including, but not limited to, mutations of the APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, DICER1, EPCAM, FH, GREM1, HOXB13, MITF, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, POLD1, POLE, PPM1D, PTCH1, PTEN, RAD51C, RAD51D, SMAD4, STK11 and TP53 genes.

The disease of viral origin that can be treated by administering the disclosed composition can include Human Papillomavirus (all strains), Herpes Simplex Virus (strains 1, 2 and 6), Simian Virus (strains 5 and 40), Hepatitis (Types A, B and C), Human Immunodeficiency Virus, Influenza A (all strains) and B (all strains) and Coronavirus (all strains but specifically including SARS, MERS, SARS-COV2, OC43 beta, NL 63 alpha, 229E alpha, HK and HKU1 beta). The disease of bacterial origin includes Mycoplasma and Tuberculosis, including MDR TB and XDR TB may also be treated by administering the disclosed composition. Other disease conditions that may respond to administration of the disclosed composition may include carnitine deficiency disorders, Antiphospholipid Syndrome, disseminate intravascular coagulation (DIC), familial adenomatous polyposis, familial adenomatous polyposis, Neurofibromatosis Type 1, alopecia areata, deafness, coloboma, nonsyndromic holoprosencephaly, Gorlin Syndrome, autism spectrum disorder, Cowden Syndrome, Bannayan-Riley-Ruvalcaba Syndrome, hereditary hemorrhagic telangiectasia, Myhre Syndrome, Juvenile and Adult Polyposis Syndrome, Tietzee Syndrome, Waardenburg Syndrome, Fancomi anemia, Blepharocheilodontic (BCD) Syndrome, Lynch Syndrome, congenital tufting enteropathy and fumarase deficiency.

Gene mutations listed in Table 2 are generally related to disorders including Non-Hodgkin's Lymphoma, B-cell Lymphoma, prostate, pancreatic, melanoma, cholangiocarcinoma, basal cell carcinoma, brain, colorectal, liver, osteosarcoma, rhabdomyosarcoma, adrenocortical carcinoma, melanoma, lung, bladder, breast, kidney (Wilms' Tumor), Li-Fraumeni Syndrome, head and neck squamous cell carcinoma. Lung, breast, ovarian, non-small cell lung carcinoma, cervical, Fanconi anemia, endometrial, glioblastomas, astrocytomas, bladder, lung, breast, skin, medulloblastoma, breast, colon, 9q22.3 microdeletion, Juvenile Myelomonocytic Leukemia, leukemia, Ovarian Syndrome, Lynch Syndrome, constitutional mismatch repair deficiency syndrome, thyroid, Hereditary leiomyomatosis and renal cell, primary macronodular adrenal hyperplasia, Turcot Syndrome, gastric cancers, primary macronodular adrenal hyperplasia, uveal melanoma and other cancers arising from mutations to genes and the related change of genetic cell signals. Such disorders may be treated using the disclosed method by administering the disclosed composition orally till the functionally of the associated gene reaches about 93-100%.

Clinical Data for Coronavirus (COVID-19)

Clinical study was performed to evaluate the disclosed composition (L-Carnitine tartrate, pyridoxine, pyridoxal-5′-phosphate, and fumaric acid). For the study eighty-six (86) subjects, all presenting with COVID-19 symptoms, were confirmed as positive for COVID-19 via PCR testing. Out of the 86 subjects, 22 subjects were found, using the same PCR test, also having MERS-coronavirus, 33 subjects has SARS-coronavirus, and 49 subjects had coronaviruss (other). All the subjects were supplemented with composition in a dose of 1,500 mg orally twice a day for a period of 2-14 days. Elderly persons with preexisting respiratory or immune system issues required the longer dosing time of 14 days. PCR tests were performed to determine the viral load. After 2-14 days of study, 62 subjects were confirmed to be clear of all the viruses present at the time of commencement of the study. The remaining subjects had no symptoms of COVID-19 infection, and no confirmatory PCR test were performed for the remaining subjects.

While the foregoing written description of the invention enables one of ordinary skill to make and use what is considered presently to be the best mode thereof, those of ordinary skill will understand and appreciate the existence of variations, combinations and equivalents of the specific embodiment, method, and examples herein. The invention should therefore not be limited by the above-described embodiment, method, and examples, but by all embodiments and methods within the scope and spirit of the invention as claimed. 

What is claimed is:
 1. A method for treating a disorder resulting from mutations in one or more genes, the method comprising the step of orally administering a composition consisting essentially of: L-Carnitine tartrate; pyridoxal-5′-phosphate; pyridoxine; and fumaric acid.
 2. The method according to claim 1, wherein the ingredients of the composition are present in a range of about: L-Carnitine tartrate—34-90%, pyridoxal-5′-phosphate—5-33%, pyridoxine—5-33%, and fumaric acid 0.5-33%.
 3. The method according to claim 1, wherein the composition is present in a form of solid dosage form selected from a group consisting of tablets and capsules.
 4. The method according to claim 1, wherein the composition is present in a form of liquid dosage.
 5. The method according to claim 1, wherein the one or more genes are selected from a group consisting of APC, ATM, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, DICER1, EPCAM, FH, GREM1, HOXB13, MITF, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, POLD1, POLE, PPM1D, PTCH1, PTEN, RAD51C, RAD51D, SMAD4, STK11, and TP53.
 6. The method according to claim 1, wherein the composition is administered in a dose of about 1,000 mg per day.
 7. The method according to claim 6, wherein the method further comprises the step of: upon administering the composition, determining a functionality of the one or more genes after predetermined duration; and administering a predetermined dose of the composition daily till the functionality of the one or more genes is in a range of about 93-100 percent.
 8. The method according to claim 7, wherein the functionality of the one or more genes is determined by polymerase chain reaction (PCR) test.
 9. The method according to claim 1, wherein the disorder is selected from a group consisting of Antiphospholipid Syndrome, disseminate intravascular coagulation (DIC), familial adenomatous polyposis, familial adenomatous polyposis, Neurofibromatosis Type 1, alopecia areata, deafness, coloboma, Nonsyndromic holoprosencephaly, Gorlin Syndrome, autism spectrum disorder, Cowden Syndrome, Bannayan-Riley-Ruvalcaba Syndrome, hereditary hemorrhagic telangiectasia, Myhre Syndrome, Juvenile and Adult Polyposis Syndrome, Tietze Syndrome, Waardenburg Syndrome, Fancomi anemia, Blepharocheilodontic (BCD) Syndrome, Lynch Syndrome, congenital tufting enteropathy, and fumarase deficiency. 